I-131 radioimmunotherapy (RIT) is showing great promise in treating non-Hodgkin's lymphoma (NHL), but there is much room for improving efficacy through effective individualized treatment planning in this and other targeted radionuclide therapies. To make advances towards this objective it is imperative that methods be developed for highly accurate tumor and critical organ (bone marrow) dosimetry. In the present application we will greatly expand the utility and effectiveness of patient specific dosimetry by developing new methods based on integrated SPECT/CT imaging coupled to Monte Carlo radiation transport calculation. The recent clinical availability of such systems combining functional imaging with high resolution anatomical imaging has opened avenues for approaching patient specific dosimetry that were not feasible with previous technology. Integrated imaging minimizes registration error and permits incorporation of CTmeasured tumor regression into dosimetry calculations. Both of these effects have been demonstrated in our previous studies to have a large impact on tumor dosimetry. The proposed methods make full use of 4D data sets to accurately calculate spatial distributions of absorbed dose. Specifically, we will 1) implement quantitative 1-131 SPECT methods for the integrated system utilizing CT anatomical information to improve reconstruction; 2) develop a voxel-based approach to tumor dosimetry incorporating tumor regression into the Monte Carlo radiation transport calculation including deformable image registration to map the changing tumor voxels; 3) develop SPECT/CT image based bone marrow dosimetry accounting for regional variations in the marrow composition as determined by quantitative CT; 4) apply these new methods to data from NHL patients undergoing 1-131 RIT imaged on the integrated system, to determine the correlation between tracer and therapy pharmacokinetics and the correlations between dose-response for tumor and dose-toxicity for bone marrow. Correlations obtained with the new methodology will be compared with those obtained from conventional mean dose calculations. With the new methods, other measures that more accurately reflect the response characteristics of absorbed dose, such as dose-volume histogram analysis and equivalent uniform dose, will also be used in the dose-response evaluations. In addition to the significance with regard to treatment planning in RIT, this research will advance the field of dosimetry in general. [unreadable] [unreadable] [unreadable]